Alopecia is the general term referring to any disease or condition involving hair loss. There are several different types of hair loss, the most common being androgenetic alopecia (AGA; see Sawaya, M. E. Seminars in Cutaneous Medicine and Surgery 17(4):276-283, 1998), alopecia areata (AA; see Fiedler & Alaiti, Dermatologic Clinics 14(4): 733-738, 1996, as well as chemotherapy and drug-induced alopecia.
Androgenetic alopecia (AGA) is by far the most common type of alopecia. AGA is a patterned, progressive loss of an excessive amount of hair from the scalp. Significant AGA occurs in 50% of men by the age of fifty and 50% of women by the age of sixty. AGA is believed to be a result of both genetic predisposition and the presence of a sufficient level of circulating androgens. It is thought that the enzyme 5 alpha reductase present in dermal papilla cells converts testosterone to dihydrotestosterone (DHT). DHT binds to androgen receptors, also localized in the dermal papilla cells, triggering changes in the hair follicle that result in (1) shortening of the anagen or growth phase of the hair cycle, (2) development of a latent phase in the hair cycle following shedding of the telogen hair, and (3) follicular miniaturization process that reduces the caliber of the anagen hairs produced. It is thought that differential expression of 5-alpha reductase and/or androgen receptors in various types of hair follicles accounts for patterned hair growth and loss.
Currently approved treatments for AGA include minoxidil (Rogaine™), an anti-hypertensive drug for which the mechanism of action in promoting hair growth is unknown. Minoxidil must be applied topically on a twice daily basis, and is therefore somewhat inconvenient to use. Studies have shown that 2% Minoxidil can provide an increase in the numbers of terminal hairs after 4-12 months (De Villez et al, Journal of the American Academy of Dermatology, Vol. 16, No. 3, Part 2 (Mar. 1987) 669-672). However, this benefit disappears over time or once the treatment is stopped. Another drug used in the treatment of AGA is finasteride (Propecia™), a selective inhibitor of the type 2 isoenzyme 5-alpha reductase. This treatment has marginal efficacy, requires daily oral administration and can have some anti-androgenic side effects such as alteration of libido. Hair transplants and scalp reduction are also performed on patients with hair loss associated with AGA. These procedures are too expensive or time consuming for many people. In addition, many people are put off by the surgical nature of the treatment.
Alopecia areata (AA) has been reported to account for 2% of new outpatients in dermatology clinics (Fiedler & Alaiti supra). AA is a nonscarring form of hair loss which occurs in humans and other species and is thought to be due to an inflammatory reaction caused by autoimmune response directed against the anagen stage hair follicle structure (McElwee et al. Pathobiology 66(2): 90-107, 1998).
A number of therapeutic modalities have been tested for the treatment of AA, with variable results ranging from no effect to partial or full hair regrowth. In some cases chronic maintenance treatment is required. Major drawbacks of these treatments are side effects, which can be local or systemic in nature. Fiedler & Alaiti (supra) and Shapiro (Dermatological Clinics 11(1): 35-46, 1993) have reviewed the various treatments available for AA, including steroids (topical, intralesional and systemic), minoxidil, anthralin, photochemotherapy, cyclosporin A and other agents, as well as combination treatments.
Photochemotherapy therapy for AA using psoralen and high energy UVA (PUVA) treatment has met with very limited success and its effectiveness for AA is in doubt (Lebwohl, M. Lancet 349:222-223, 1997). Side effects of PUVA treatment such as nausea, pigmentary changes, risk of skin cancer formation, and cataracts have been reported (Fiedler & Alaiti, supra). Antioxidants have been used to ameliorate the side-effects of PUVA therapy (Ptapenko & Kyagova, Membr. Cell Biol. 12(2): 269-278, 1998). The use of 2% khellin, a compound with a chemical structure that resembles psoralen, and UVA for alopecia areata was found to be successful in 5 of the 10 patients tested (Orasa et al. Int. J. Dermatol. 32(9): 690, 1993). Since khellin did not cause phototoxicity, the authors have suggested its use as an alternative to psoralen.
Hematoporphyrin and high energy UVA has been used in a very limited study by Monfrcola et al. (Photodermatology 4:305-306, 1987). Two patients were treated with topical hematoporphyrin (0.5%, HP) and UVA irradiation with three times a week for eight weeks. In the first week of treatment there was significant erythema and mild scaling followed by hyperpigmentation in the HP treated sites. Side effects included unpleasant reddish skin coloration for several hours and sometimes burning sensations during the irradiation phase. The authors point out that severe phototoxic reactions could occur with the use of HP concentrations greater than 1%. They also state that more work is needed before this approach can be subject to routine clinical use.
Photodynamic therapy (PDT) has been utilized for the removal of unwanted hair in human subjects. Briefly the treatment involves a topical application of a photosensitizer on a selected area of the skin, a period for absorption of the photosensitizer, followed by a pulse or continuous irradiation or vibration of the area. The process involves inactivating or destroying the hair follicles or destroying the tissue feeding the hair follicles (see U.S. Pat. Nos. 5,669,916; 5,871,480; WO 97/32046).
Photodynamic therapy is a minimally invasive two-step medical procedure that uses photoactivatable drugs called photosensitizers to treat a range of diseases. First, a photosensitizer is administered and, once it has permeated the target tissue, the photosensitizer is then activated by exposure to a dose of electromagnetic (usually light) radiation at a particular wavelength. Photodynamic therapies have been approved for a number of indications including the treatment of non-small cell lung cancer (Photofrin™), age-related macular degeneration (Visudyne™), actinic keratosis (Metvix™, Levulan™), and basal cell carcinoma (Metvix™).
There continues to be a need for an effective, non-surgical procedure that results in a rapid increase in the number of terminal hairs but has minimal side effects.
Citation of the above documents is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.